Effectiveness of Pre-exposure prophylaxis (PrEP) in reducing the transmissions of HIV virus in heterosexual Sero-discordant sexual encounters. A systematic literature review

HIV Prevalence

In today’s world, approximately 35 million individuals living with HIV. HIV prevention is on the rise by use of the following methods; condom barriers for both male and female, male circumcision, at the hospital vigilant use of sharp objects such as needles, to avoid viral transmission, correct use of disinfection processes, at the aggressive delivery use of hindrance of mother to kid infections. Mahapatra, 2016), claimed that the new HIV infections incidence has been on the rise since 2008, a predictable 2.9 million persons were once more infected. There is an alarming need to grant safe methods that have been proven to be useful to achieve prevention of HIV and AIDS. Among the newly infected persons are the serodiscordant partners who are either married or at the young stage. The partners (one infected with HIV and another one not), are said to be at the highest risk of being infected. However, due to researchers understanding the biology of the disease and the introduction of the preventive measures, the infection risk among the couples has been reduced to deficient levels. According to Okwundu, et. al. 2016, prevention of HIV in serodiscordant couples maybe easier than in other types of relationships, for instance, casual relationships and seroconcordant couples, this is due to awareness and strict adherence on the prescription (Okwundu, et. al. 2016).

PrEP is a treatment modality that uses medicine to prevent infections of HIV in people who are already exposed to the virus. It uses antiretroviral medication to stop the HIV infection acquisition by healthy individuals. There is evidence from research by use of laboratory animals and also in the clinical studies among human, where the use of antiretroviral therapy by pregnant women has been shown to prevent the babies from getting infected with HIV. As of now, there are HIV negative babies who have been born to HIV positive mothers. One of the key drawbacks to consider is the safety of the drugs being used as antiretroviral therapy in such patients. For PrEP to be effective the side effect profile of the drug must be one that can be tolerated by patients. Drugs such as tenofovir and emtricitabine have been shown to be safe following clinical trials as indicated by Mahapatra, 2016.

The initial trial to generate the study outcomes was the iPrex experiment. The experiment involved a multi-phase-3 clinical research which examined if the daily combination of the emtricitabine and tenofovir were possible to efficiently and safely prohibit the transfer of HIV infection among the gay men as well as the bisexual women. Approximately about 46% reduction by using the improved target-treatment analysis in the transmission of HIV was recorded. However, the observance of this regime was found to be lower than the anticipated in the various countries. The trial was done in 2010 in the human being to produce sounding statistical facts about PrEP. The test was done on gays, and they were given oral pill as well as placebo, and it was noted that the oral introduction reduced the HIV infection by 44% this is according to Kim et al. 2010 findings. Recent research by Straub et al. 2017, shows that Men who are reported to consuming the pills in about 90 percent or even additional days recorded a 75% efficacy of the PrEP use. Resistance was conversely found among 3 participants who showed an existing severe infection of HIV which was undetectable at the baseline and randomized to active medicine. A marked tendency in the line of risk drug minimization, especially the escalated condom utilization and the decreased amount of couples was reported in all sites (Snowden, et. al. 2017). The second research as shown by FHI, (2011) which was used to generate the grades was the experimental study regarding the daily tenofovir and emtricitabine among the high-risk women of African origin. However, the study was dismissed due to the insufficiency of the infections quantity in the placebo arms with the PrEP usage.

The 3rd trial was conducted by U.S CDC and by The Botswana ministry of health this was done on daily oral emtricitabine, and tenofovir consumption in both men and women by CDC, (2011) .the results of this research study gave out an indication that the infection reduced by up to 63%. Another research which is the fourth one was done in Kenya and Uganda. This was a daily orally taken regime of emtricitabine and tenofovir in HIV-1 serodiscordant partners. Mujugira et al., (2011) found that those who took tenofovir only had fewer HIV infection by 62%, those who received emtricitabine with tenofovir had reduced the disease by 73% than those who had a placebo.

The above systemic study has raised concern on, should TDF or TDF plus FTC be taken daily by the serodiscordant couples in preventing HIV infection?

Since several studies have been done, trials have shown that for the PrEP to work efficiently, the dose should be taken correctly and as prescribed, if a person misses taking the dosage accurately, as per the dosage pattern, he/she is likely to increase the risk of infection. According to BBC, 2017, THE DRUG HAS BEEN KNOWN TO REDUCE HIV infection to nearly zero. Nevertheless, PrEP cannot prevent one against infection by STDs and STIs BBC, 2017).

Earlier before 2015 PrEP was being used only by specific consumers just who are infected by HIV, not until WHO recommended the use of the drug by people at risk of contracting it. This had benefited the worldwide population and has reduced the risk of infection to anyone unlike previously when it was only targeting, sex workers, versus men sex, and drug users by injection mean as by the UNAIDS, 2016).The united nations general assembly is targeting to provide 3M people at risk of HIV contraction with PrEP by or before the end of 2020. However, this initiation has recorded about 100,000 people who are the beneficiaries by October 2016. The majority of the recipients are in the USA. The activities of Prep are continuously increasing worldwide with minimum beneficiaries outside the USA. The drugs tenofovir and emtricitabine in the form of the single drug Truvada is the very recent drug known to be a preventive measure against HIV.

Kim et al. 2010 found that, in the early years, there was the use of traditional interventions, which was proved to be inefficient, this is what led to more research on other means of prevention (Kim et al. 2010). Recently the use of prep orally as well as topically is promising success in prevention measures.

Evidence Base

Numerous RCT studies have proven the efficiency of PrEP when a combination of FTC/TDC uses or when only the utilization of TDF to prevent it is used. The approach has been indicated to reduce the rates of the disease spread among the sexually active women and men in the study conducted in Botswana which a country has known for its HIV infection burden. Similar results were found among the heterosexual partners living in the East African region, as well as the IDUs of Thailand (Shattock, et. al. 2011). The Cochrane investigation of these researchers revealed that the comparative danger of obtaining HIV involved 0.48 (94% interval of confidence, 0.27-0.84) for persons consuming FTC or TDC and o.34 (94% interval of confidence, 0.23-0.56) for the ones only taking TDF as per Mahapatra, 2016, findings. The result of these studies, however, did not indicate any statistically substantial dissimilarity in the difference of HIV prevalence among the groups of persons consuming the FTC/TDF as compared to the individuals using TDF alone (Mahapatra, 2016). Previous results from the successive open-label reviews propose that PrEP is efficient and the adherence to its use is great in practical life and the investigational backgrounds.

The advantages of PrEP in feminine patients who do not utilize the antiretroviral medicines are however minimally clear. Young et al. 2017 said that the various randomized control tests in several locations around Africa further failed to indicate the substantial statistical minimization in HIV frequency between the women who use PrEP on a daily basis (Young et al. 2017). Other two studies examined the utilization of the post and pre-coital tenofovir vaginal gel where only one research led to the discovery of the significant impact of HIV infection incidence.

When PrEP is taken orally in a combination of TDF and FTC (Truvada), it shows a high reduction of viral infection. Additionally, it has been noted that prep might be less forgiving in male than females and that STDs are modulating the efficacy of the prep. Pharmacometrics model is being generated to assess the relationship between prep efficiency and gender.

The Finest Candidate for Pre-exposure Prophylaxis

Pre-exposure prophylaxis is known to be effective for the avoidance of HIV. In 2012, US FDA (Food and Drug Administration) approved that, Daily uptake oftenofovirDisoproxilFumarate and emtricitabine (FTC/TDF) for the HIV prevention amongst adults. In 2014, the US, CDCs (Centers for Disease Control and Prevention) recommended the use of TDF as the better-approved method of HIV prevention. Mahapatra, 2016 argued that Pre-exposure prophylaxis can prevent up to nearly 100% infection (Mahapatra, 2016). It includes homosexuals and women and men who are heterosexually active. For gays, pointers to Pre-exposure prophylaxis comprise of participating in anal sex without the use of a condom, possessing multiple sex partners, recent Sexually Transmitted Infection that is bacterial and having a sexual partner infected with HIV. Indications for heterosexual women and men include participating in condomless sex with partners who are highly susceptible to HIV infection and having an infected sexual partner. People who inject drugs portray risks such as having injecting partners who are HIV-infected, injecting medications while undergoing drug treatment and sharing injection equipment. Concerning the 1.2 million Americans having signed for Pre-exposure prophylaxis, only about 100,000 have received a prescription. To identify Pre-exposure prophylaxis culprits in healthcare settings, a sexual history is taken followed by a non-condemnatory and open-minded interrogation about drug and sexual behaviors. Nevertheless, this account is not always acquired. Additionally, many beneficiaries of Pre-exposure prophylaxis are not aware of the risks they expose themselves. To increase knowledge of providers to address sexual health of patients better, National Network of Sexually Transmitted Diseases Prevention Training Centers has unveiled courses to equip the providers. The providers, as well as their clients, can now use online tools to assess individuals’ risks. Zarwell, 2016 found that A better platform is the Sex Pro which lets individuals answer questions about their behavior then converts the answers in the form of a score that makes them know how they are protecting themselves against infection by HIV-infection (Zarwell, 2016).

However, these tools and guidelines are not sufficient enough to identify the beneficiaries of Pre-exposure prophylaxis. It is, therefore, crucial to take HIV observance and native epidemiology into consideration in drug and sexual by use of networks. For example, black homosexuals are more stuck by STIs and HIV despite having similar or inferior risks at individual-levels. Acceptance of Pre-exposure prophylaxis in black gays is lower than in the whites as investigated by Zarwell, 2016). The case also applies to women primarily due to incomplete awareness of Pre-exposure prophylaxis among them and their providers. Providers should, therefore, consider demographic factors to address health differences. Additionally, due to feeling uncomfortable in disclosing HIV risk behaviors by some patients, the prescription should be granted to only those who request for it.

The Standard Evaluation

Providers should evaluate patients’ interest and knowledge in Pre-exposure prophylaxis (PrEP) through the inclusion of a description of how PrEP works especially the likelihood of passing syndrome identified through gastrointestinal indicators that appear after weeks and bone toxicity and renal risks. The patients’ last exposure to HIV should be determined and assessment of signs of HIV infection done. Health practitioners ought to record a counteractive HIV antibody test before starting the PrEP which can be combined with HIV test. Higgs & Green, 2011 argued that, due to the lower sensitivity of oral examinations, rapid verbal tests should not be used to test for HIV infection (Higgs & Green, 2011). Other providers acquire an HIV RNA test especially for patients with current exposures. For high suspicion of acute HIV, PrEP should be postponed till HIV RNA results are ascertained since introducing PrEP through acute HIV can result in the growth of mutations which offer antiretroviral resistance. Renal function should be determined, and tests conducted for infection with hepatitis B and C types. PrEP should not be given to patients with a creatinine permission of 60 ml per minute. Re-energized HBV infection can lead to hepatic damage. As such, patients’ hepatitis B status should be noted to ensure that liver function is monitored correctly. It should be noted that hepatitis B is not a concise indication of the usage of PrEP. Providers ought to assess for risk factors for renal ailments. They should further screen patients for chlamydia, gonorrhea, and syphilis and at extra-genital parts since a bulk of extragenital infections are asymptomatic (Straub, et. al. 2017). Johnsen, et al. 2017) argued that women being introduced to prep should be tested for pregnancy and counseling should be offered to patients regarding adherence and optimization of PrEP. Immunizations for vaccine-preventable Sexually Transmitted Infections should also be provided (Johnsen, et al. 2017). The main aim of the prep is to achieve protection against an increase in the concentration of HIV in the infected cell. This can be achieved through the fight by the immunity in combination with other prevention measures. Prep efficacy is shown to be excellent in miming the multinational iPrEx study (Semprini, et. al. 2013).

Semprini et al. 2013 indicated that in cases where an HIV positive lady is opting to conceive from an HIV positive man, prep has also been proved effective in preventing infection (Semprini, et. al. 201). This has been achieved through ART treatment of HIV partner then orally dosage of TDF/FTC by the woman for a month before conception, then the introduction of the processed sperms from the partner. Alternatively, a limited unprotected sex at a fertility period of the woman can be applied.

CHAPTER THREE: METHODOLOGY

Study Design

The main reliable sources of information for this dissertation were secondary data. Research conducted by global medical research center formed the basis of this study. The project was determining the uptake, use, and effectiveness of pre-exposure prophylaxis for HIV negative individuals. Related to this study were several other types of research for instance, those investigating antiretroviral prophylaxis for HIV prevention amongst heterosexual women and men. In another research conducted by AIDS-London, the study was based on determining safety and effectiveness of pre-exposure prophylaxis of HIV across different populations. A study conducted by Emory University department of medicine, division of infectious diseases on the other hand also formed part of this research while an abstract from the national institute of health did provide vital information for this research tool. The research encompassed the HIV prevention. Furthermore, the research carried out by a team from the center for YRG on AIDS Research and training profoundly contributed to the compilation of this report. The research was assessing the risk dynamics for the transmission of HIV between discordant heterosexual individuals based in south India. In addition to the findings a research conducted by from the Center for Global Health, Massachusetts Department of Medicine were evaluating the current conception for PrEP adherence among different populations.

The different methods deployed in investigating the above research works are as described below.

1. Research based on effectiveness, uptake, and use of PrEP for HIV negative individuals and who dwelled with HIV positive persons.

Study Population

The project was based in East Africa in two countries; Kenya and Uganda and was completed in 3 years. HIV care centers were deployed in Thika and Kisumu in Kenya and kabwohe and Kampala in Uganda to deliver the intervention. These clinics were involved in the engagement of HIV prevention research before.

Delivery

The delivery model was such that PrEP was incorporated into HIV treatment services whereby PrEP was prioritized for partners who were HIV negative and were in a serodiscordant relationship before during the initial half a year period after the partner living with HIV incorporated antiretroviral therapy (ART). MEMS bottles (medication event monitoring system) were used to measure adherence to PrEP. In addition to this plasma samples from randomly selected participants were subjected to quantification of tenofovir. Concrete interventions were deployed so that implementation strategies employed in the clinics would ensure delivery approach would be efficient.

HIV serodiscordant couples were selected from events such community outreach or referrals from VCT centers (voluntary counseling and testing centers). Other referrals included ART and antenatal clinics. The couples were of more than 17 years of age. Besides this, they were sexually active and were supposed to continue as partners for at least 12 months. When the couples were being enrolled, the couples who were HIV-negative had not at any moment utilized PrEP. Their medical results indicated a normal function of the renal organ; pregnancy test was negative with absence of the hepatitis B virus infection. The HIV positive spouses did not use ART at the time of enrollment. Spouses were omitted from the study if the HIV condition was acute and needed the immediate use of ART.

Study Procedure

Couples were to have study visitations together for 24 months whereby a series of couples-based HIV prevention strategies such as the management and supervision of the STIs (Sexually Transmitted Infection) as well as the use of condoms were delivered.

Participants were required to undergo monthly visits, which included indulgence of 30 medication study days and the gathering of the previous month’s unutilized mediation, assessment of any side effects experienced, individual’s adherence counseling and HIV-1 testing.

Pregnancy would be tested in women on a monthly basis, and if there were a case of pregnancy, study medication would be withheld from the women and they, would be referred to receive antenatal care. This ensured the safety of the unborn child. They would be allowed to continue with the study medication after the pregnancy period was over.

The way in which PrEP was delivered is as follows; PrEP was provided to all the HIV-negative members in the form of co-framed tenofovir/emtricitabine disoproxil (TDC/FTC).Streamlined messages were used to ensure adherence to PREP focusing on individual’s challenges to day-to-day usage and ways in which these problems would be overcome.

It was ensured that ART was available in the clinics at the start of the study for all participants who were HIV positive. A CD4 count was conducted and found to be less than 350 cell/uL. ART was delivered to members through community hospitals. Before the study, each HIV, positive person was assessed for a count of CD4 and also during follow up which took place at an interval of 6 months. The individuals who were subject to the study and were using PrEP were advised to terminate PrEP use after their partner living with HIV had used ART for not less than six months.

This strategy of using PrEP for a limited time by the HIV-negative partner till the partner living with HIV had used ART for at least six months was included in the counseling discussions. In some situations, the counselor would advise the HIV negative partner to continue with PrEP such as when ART was not adherent or HIV status was unknown within the partners or couples were having intentions of pregnancy.As indicated earlier MEMS caps (medication event monitoring system) were the primary measure of adherence. They recorded all openings of PrEP pill bottles where self-reporting pharmacy pill counts were collected from participants during their visitations. The level of adherence which would be sufficient to protect against HIV transmission was measured in two ways which were a dosage 4 and six pills a week. If couples were reported to have had less than 100% condom use before six months use of ART, then the risk of acquiring HIV was high. If there was 100% use of condoms, then the risk was low otherwise if there was no sexual activity the risk was very low.

HIV negative partners were tested for HIV at each follow-up visit to ascertain any incidence of HIV. Immunoassay enzyme (EIA) and HIV RNA quantification enzyme were used to confirm the results of the tests conducted. If seroconversion were confirmed the Seroconverters that were approved, samples would then beer quantified for HIV RNA. If samples were positive for HIV RNA, it was presumed that the samples had been infected before the start of the project and if the samples were negative for HIV RNA it was concluded that they comprised of incident infections. HIV resistance was detected using archived plasma samples \. Also, to determine the incidence of seroconversion samples from the HIV positive partner would be sequenced together with the HIV negative partner and a phylogenetic analysis done to assess if the infection came from the partner under study.

2. Research on anti-retroviral prophylaxis for HIV-1 prevention among couples who are in serodiscordant relationship heterosexual men and women.

Study Procedure

The research was undertaken in Kenya and Uganda and it comprised of heterosexual couples where one participant was HIV positive. The partners that were HIV seronegative were randomly assigned to tenofovir (TDF), a combination of emtricitabine/tenofovir (FTC/TDF) and placebo. A follow up then took place monthly for 36 months. This follows up constituted HIV testing, adherence counseling and assessment of any side effects experienced. A CD4 cell count was also conducted on HIV positive partners after every six months.

3. The following study conducted by AIDS (LONDON) the study design was through systematic review and meta-analysis.

The study was based on secondary data, and the outcome of this methodology included resistance for ART drugs, HIV infections, and concerns on reproduction well as behavioral characteristics (use of condoms and how many sexual partners a person has).

4. From the study conducted by Emory University and the University of California on HIV pre-exposure prophylaxis for women, clinical trials were conducted to investigate the delivery of HIV acquisition in women. The trials conducted showed the efficacy of PrEP in the reduction of HIV.

5. Below is a description of how the research that was assessing risk factors for HIV transmission among heterosexual discordant couples was conducted.

The study population comprised a cohort of serodiscordant couples who sought medical attention at Education and Aids YRG center (YRG CARE). Through clinical visitations, patients were engaged in interviews about sexual risks and protective behaviors as well. Partners that were not infected with HIV would then be assessed for HIV status at every visit, and this would take place every three to six months. Partners who were living with HIV-positive would complete a survey that was assessing adherence to ART for three months usage of condoms with their primary partners in the previous months and also the rate of alcohol consumption. Through the clinic visitations partners were counseled together concerning STIs and strategies that would reduce risk. At enrollment, all patients that were infected with HIV blood samples were taken and tested for HIV. The critical features that were captured in the research include population and clinical traits, CD4 cell count and also plasma HIV-1 RNA loads. In addition to these sexual behaviors was also assessed. These features were evaluated at enrollment and longitudinally during follow up for a period of more than 12 months.

6. The research that was based on current features for PrEP adherence described methods to aid PrEP adherence and the current ways in which adherence to PrEP is perceived. This review was based on different demonstration projects and clinical trials that had been already conducted earlier. Projects such as iPrEx, IPERGAY and VOICE were some the researchers that were used.

Results

For the research based on effectiveness of PrEP for HIV negative persons with partners living with HIV descriptive statistics was used to summarize the traits of the couples and trends of PrEP use. The total number of couples that were deployed for this study were n=1010. More than a quarter of the couples showed characteristics that indicated high risk for HIV transmission, that is, 41%(n=414)of the couples living with HIV concentration of HIV RNA was>50000copies/ml and 65%(n=657) reported to having not used condoms during sex in the previous months.

More than half of the couples (66.7% n=674) the HIV- negative partner was male and 67% (n=452) of these males had not been circumcised. About 94% of the enrolled couples were married (n=954). The median for the time the couples lived together was 2.3 years. Very few couple knew their HIV discordant status given the median time know in years was 0.1.About 97.1% of the participants who were negative used PrEP including the 95%(n=960) that at enrollment were introduced into the project. Median time for PrEP usage was 12 months with an interquartile range of 6-18. Of the participants 81 % (818) that were HIV- negative used PrEP until their HIV positive was entirely dependent on ART. This included the 535(51.3%) who used PrEP for 6 months after their partner has initiated ART use. Due to fertility desires in some partners, about 15.5% (n=114) of PrEP users used PrEP for more than 6 months. Other reasons that accounted to usage of PrEP for at least 6 months was pregnancy (41%). Partners who were HIV negative and were not using PrEP were 28and 89 % (n=25) had partners living with HIV and were using ART. Those that were not protected by PrEP were 0.3 % (n=3). Since the partners were HIV negative.

The tables below give a summary of the descriptive above.

Table 1

Table 2

Table 3

Table 4

Table 4.1

The table below displays the recommended medication for oral PrEP.

The flow chart below gives a clear view of how the couples that were initiated to the study responded to the methods that were deployed during the study.

Fig 1

The table below shows the expected results as compared to the HIV observed incidence.

Before the HIV positive partners used ART for 6 months, PrEP was provided for partners who were HIV negative and were 602.4 persons-years (64.9%). When PrEP was not dispensed partners living with HIV and did not engage in sex activity were reported to be 46.6%.

From a sample of 140 individuals selected for TFV quantification after PrEP was offered to the participants, 81% (n=113) had TFV detected. MEMS data indicated that there was high adherence. The percentage by which adherence was achieved in the participants was 75-88%. This was sufficient to reduce the risk of HIV acquisition. Pharmacy pill counts showed that 87% and 96% of the bottles had more than 80% and 50% respectively of the expected doses taken.

About 80.7 incident infections would occur if interventions were not deployed. This resulted in a 4.75 per 100 person-years incidence. It was found out that the intervention was effective in the categories engaged, that is effectiveness was 93% with a p value being < 0.0001, those that were HIV negative and were less than 25 years, effectiveness was 94% and couples with HIV partners who were HIV positive and HIV RNA was more than 50000 copies/ml at baseline. The effectiveness was 95% with a p =0.0001.

Status of Art Within Couples

The chart below is an indication of the status of different couples after follow up. Notably, 75.4 %( n=762) of the couples who were on ART, their viral load was indicated to have been suppressed. Less than a quarter of the couples (11.4%, n=115) their status on ART use was documented as unknown. Serodiscordant partners who did not have a viral suppression known were 8.22 %( n=83). Partners living with HIV and did not use ART were 4.6 %( n=46). Very few couples, that is 0.39 %( n=3) were on ART and their viral level was unknown.

A statistical summary constituted from the research describing antiretroviral prophylaxis for HIV prevention among heterosexual men and women is as below.

The total sample size was n=4758: these were the couples enrolled for the study and from this 62 %(n=2950) the HIV negative partners were male. Those that were selected for TDF were 1584, 1579 for FTC/TDF and 1584 for placebo. The median CD4 count was 495 cell/ul with an interquartile range of 375-662. Depending on which drug was deployed, the following are the percentages by which relative HIV-1 relative incidence was reduced; 67% for TDF and 75% for FTC/TDF. The protective effects of the two were not significantly different since the p-value was 0.23(< 0.05). Both medications greatly reduced incidence of HIV-1 in both genders, male and female.

The chart below shows the median CD4 count for the different drugs that were used.

Below is a summary of the results of the study conducted by AIDS (London)

Drug resistance

Trials that were conducted showed that 18 %( n=8) HIV infections there occurred 44 cases of individuals with TDF or FTC resistance. Comparison of PrEP with placebo, it was noted that FTC and TDF mutations presented a higher risk in PrEP. The risk ratio was 3.34, with 95% CI: 1.11-10.06 and a p value of 0.03.

HIV Infection

From the results it was observed that HIV infection was reduced by 51%. Regression results indicated adherence of PrEP effectiveness was significant. The regression coefficient was -0.02(p=0.001). It was clear that PrEP was most efficient in findings that had high adherence. This was from the 70% reduction with a risk ratio of 0.3 It was noted that there was a reduced infection risk in cases where the level of adherence was moderate risk was still high for low adherent studies with a risk ratio of 0.95. When PrEP was compared with placebo the HIV relative risk for infection for rectal exposure was 0.34.Penile or vaginal exposure had a coefficient of 0.54(95% CI 0.32-0.90, p=0.02). There wasn’t a considerable significant difference between sexes and dosing. Results from study conducted by Emory and California universities department of medicine had the following results:

From the clinical trials, it was observed that randomised clinical trials demostrated efficacy in PrEP use in reducing HIV. There was a relatively significant reductions indicated by 62% reduction in heterodiscordant couples.A study conducted in botswana indicated that efficacy of daily oral TDF/FTC in about 49%(n=557) of the women in the study there was reduced statistical power.

In regard to safety in use of prEP long term effects are usually expereienced as observed through kidney and bone toxities. In this regard, PrEP contained in TDF usage for a period of more than 36 months as associated with a small amount decline in glomelurar filtration rate. There is a high probabilty of women facing risk of osteoporosis than men.

Basing the results from the research assesing the riskof HIV among heterosexual couples the incidence of HIV infection per 100 persons in an year in HIV negative partners who were enrolled at the beginning of the research was found to be 6.52. Discordant patients were more involved in highly active antiretroviral therapy(62.9%) as compared to those that were in seroconverting relationships(42.9%). A p value of less than 0.05 indicated that significantly patients that were in seroconverting relationships had higher plasma viral loads than patients that were in a discordant relationship. Statistical results indicated that patients that were in seronverting relationships would rarely use condoms in comparison to those that were in discordant relationship.

From the review of current concepts for PrEP adherence it was indicated that clinical trials yielded a PrEP efficacy of 0-75%. This was as a result due to the differences in adherence. Results showed that the overall median number of pills according to the pill count taken monthly were only 16. Efficacy was found to be 82% and this suggested that those that are at high risk of contracting HIV are the ones taking PrEP when needed.

Discussion

About the research on HIV-negative persons’ pre-exposure prophylaxis with HIV negative counterparts; effectiveness uptake and use conducted in East Africa, PrEP adherence and uptake was high, and incident of HIV was eliminated virtually. PrEP was dispensed on an average of 12 months for the 1010 healthy persons who were examined for two years. Guidelines for ART have been more involving, and the usage has been standardized for HIV positive people. Such an occurance may probably result in a reduced regular PrEP usage duration as the period between analysis of HIV and ART commencement is diminutive for spouses that are HIV infected (Mujugira, et al. (2013). Earlier most couples would dissolve their partnership with their HIV-positive counterpart before PrEP was introduced or they were entirely dependent on ART for protection. It was attributed that most of the women who were infected with HIV acquired the causal agent from their male companion or a main male partner. Findings indicated that HIV frequency was 2.54 incidences per a hundred persons for ladies who were in a stable relationship. In comparison to other findings, this incidence was high indicating a low use of condoms in a primary relationship. The incidence was compared with infections acquired through casual male partners or commercial sex workers. Besides male to female transmission, there is also female to male transmission. In the US, for example, it is estimated that about 40-60% of individuals in a serodiscordant relationship are females that are HIV-positive, but the incidence of HIV transmission is not that high

The study was aiming at introducing e delivery of PrEP couples for avoidance and endorse PrEP termination immediately the HIV infected partner pledged and continued ART. After two years of follow up 75% of the couples enrolled depended on viral suppression and ART as well in the infected partners for safety against the spread of HIV. About half of couples that were enrolled and were HIV negative implemented the PrEP strategy. PrEP was used until the companion who was HIV positive had endured a 6-month period of ART. Some participants used PrEP for a longer period and others for a shorter period which led to overlapping with ART. The instances provide the basis for the feasibility to implement PrEP strategy and also its integration into an existing clinical structure. Clinical trials have shown low adherence for PrEP as compared to demonstration projects that have had a greater adherence, because in demonstration projects there are messages which describe the efficacy of PrEP and this strategy is usually applied in community clinics thus highly known than the clinical trials (Okwundu, 2012).

Notably, there is need to sensitize youths particularly those that are yet to get wedded to the relationships changing nature to inspire communication that is open with counselors and counseling be based on realistic prevention strategies. Through PrEP intervention, serodiscordant couples were more engaged with health care and primary prevention strategies. Couples were enlightened on ART and clinical care and this enhanced their know-how on ART programs as well as initiating ART in a faster way. This approach provided support to the partners as a unit and as an individual as well. It is evident that without PrEPep use, the partner living with HIV should be dependent on condoms for core prevention until a time when ART will be initiated. Factors such as desires for pregnancy, cultural norms and hitches in handling discordancy tend to discourage condom use within marriage.

An intervention of prep has brought positive outcomes in relationships. This include improved stability in a relationship and strengthening negotiation skills and communication between couples. It provides couples with a basis to discuss very crucial information which includes plans for pregnancy, discussing sexual behavior, concerns about HIV risk as well as topic discussions relevant for reducing HIV risk. It was attributed that this mode of delivery is cost-effective since most of the PrEP users that were in the study required PrEP for a short period until viral suppression and ART use could be the main measure of protection from HIV. With future evaluations and delivery programs improving efficiency for patients will enhance effectiveness reduce cost. These programs should be tailored in such a way that it will be possible to estimate how frequent PrEP is restarted and also the cost implications.

Drug levels are measured to determine adherence rate to the PrEP usage. Adherence, in this case, was measured through MEMS caps and laboratory markers which were the major research tools. They are not ideal for societal clinics due to their logistical and cost requirements. Despite these challenges, HIV load testing programmatic scale-up is on implementation, and this will provide guidance on prevention of transmission and ART adherence as well as reinforcing information about PrEP observation when the viral capacity is not inhibited. To ensure a successful implementation of PrEP, there is need to ensure a sustained adherence. There are indications that young women especially who are unmarried and are sexually active usually find it difficult to maintain PrEP adherence, for example, about 80% stated that they rarely remembered to take a pill and if they did it would be about two days in a week but those that are in serodiscordant relationship usually maintain high adherence levels.

It was noted that the delivery of PrEP to healthy participants with spouses that were HIV infected was highly effective. The participants that were HIV negative used PrEP and most discontinued after a sustained use of ART by HIV positive counterparts and this transferred their HIV safety knowledge to their mate’s ART usage.

Programs such as messaging and provision of materials designed for couples need to be deployed for PrEP to be delivered to couples as a package of ART. However, this can be supplemented by the provision of locations for PrEP issuance to tailor services to diverse subpopulations. The methods would help individuals understand and assess their risk accurately. Self-Assessment of HIV risk acquisition can be challenging since it requires understanding on the modes of HIV transmission, clear view of an individual’s behavior and has enough information concerning the behavior of their sexual partner. Adherence was noted to be high in situations where the serodiscordant partners indicated they wanted their relationship to succeed. Also, those that were pregnant or wanted to get pregnant had high adherence to PrEP. The factors (pregnancy and maintenance of a relationship) may serve as efficient components of the message conveyed during counseling rather than sensitizing the relationship between adherence and efficacy. It was evident that most participants adhered better when they needed protection against HIV infection.

The observed phenomenon was as a result of the PrEP adherence being statistically significantly high when partners engaged in sexual activities. Through evaluation of individuals concern on taking daily PrEP, it is possible to identify individuals where PrEP is most feasible.If the partner living with HIV is reported to have a low adherence to PrEP after more than six months then this is in line with the fact that PrEP was needed for a limited period that is, it acted as a bridge to ART. A consistent use of PrEP is needed so that protective tenofovir levels can be achieved. It is because participants who would frequently start and stop using PrEP have a major challenge since they will still be at high risk for HIV infection. Support to adherence needs to be deployed in situations where adherence was low. Additionally, it was observed in young women mainly those that were less than 25 years and also to individuals who use PrEP for a prolonged period (more than six months). Clinical visits have proven to be the most effective mode which has benefited both partners. In spite of findings indicating high adherence for PrEP, there are findings that indicated that participants were at a high risk for HIV infection as a result of insufficient adherence. These findings suggest the need for PrEP interventions or guidance for effective use of HIV prevention strategies such as condom use.

A descriptive summary of the study conducted to determine the safety and efficacy of verbalized HIV pre-exposure prophylaxis for the entire participants is as follows;.PrEP was in effect in decreasing HIV acquirement and transmission risk through PrEP dosing schemes and regimes as well as sexual exposure. Through research, suggestions are such that there is a possible biological framework for diverse protection rates conferring to main transmission routes. There is the high rate of drug concentration in the rectal tissue as compared to vaginal tissues since PrEP reaches the rectal tissues much faster and also stays longer in the tissues as compared to vaginal tissues. The analyses suggested that trial-level devotion regulated the PrEP’s impacts on the acquisition of HIV since PrEP was more efficient in plummeting HIV infection with greater levels of PrEP observation. The level of effectiveness was similar across all proportions of people who had PrEP detected, and it was concluded that prep was efficacious when used. For heterosexual populations, TDF PrEP is considered attractive due to its effectiveness, availability, lower risk of drug resistance and its lower cost. Results demonstrated that adolescent girls can uphold greater levels of the PrEP use upon acknowledging the PrEP effectiveness. In addition to this women are more adherent to PrEP

Regarding the safety of PrEP, there were no cases of adverse conditions though two studies indicated the slight decrease in the function of the renal organ amidst the persons taking PrEP. Intensive monitoring of renal function has been deployed in PrEP programs which include frequent creatine testing as a safety measure. Also, there were cases of the small decrease in bone mineral density among African women of PrEP use which were terminated after that. HIV illness taking place due to lack of PrEP would need constant antiretroviral therapy, and this is related to a 3- 5 much loss of the mineral density of the bone matched with PrEP use (56). Furthermore, HIV has an undeviating toxicity to the bone thus providing a substantial risk to value proportion.

A resistance of FTC or tenofovir throughout utilization of PrEP was minimal. Contributors randomly selected for PrEP showed greater resistance risk than the placebo amid the ones who were acutely HIV positive at the time PrEP was being started. There existed several instances of opposition to TDF than FTC. This complied with the results from partners of the PrEP study continuance which directly equated the regimens. During the follow up study, married participants were advised not to share the medication offered during study since the dual or mono agent ARV (Antiretroviral) therapy cannot lead to a prolonged virological suppression which could result in resistance to the PrEP especially to HIV positive partners. Risk of the drug disapproval regarding the PrEP was to be assessed with general remunerations. It was evident that if PrEP were withheld cases of HIV infection would have increased and this would require constant psychotherapy with an annual report drug risk hostility ranging from 5 to 20% though in a recent study conducted among PrEP users reported that there were high number of STI reported cases and a 41% decrease in the use of condoms. PrEP appear not to have any effect on hormonal contraception effectiveness about pregnancy. Use of mouth PrEP was not linked with severe augmented impacts on pregnancy between ladies that were consuming PrEP during the initial stages of pregnancy.

The study that was based “antiretroviral HIV prevention prophylaxis amongst heterosexual women and men” had the following key notes; it was noted that 67% and 75% participants living with HIV and were using oral TDF and FTC/TDF respectively had been protected against HIV-1 as compared to other HIV hindrance services. TDF and FTC prove to be efficient and safe in the African population based on the research conducted. A systematic review indicates that TDF and FTC+TDF ascertained to be efficient compared to the placebo in male or female. The results also showed that they were more effective in men as compared to women but statistically this difference was not significant. Pill count adherence and retention as well was noted to be high. Tenofovir was detected in 82% of the samples from participants that were randomly selected, and tenofovir was recorded to have a more than 85% protection from HIV-1. It was established that trust relationship support within serodiscordant partners usually enhanced high adherence. There is need to establish strategies besides the one set in a clinical setting to achieve a high adherence. About 25% of the participants who had acute HIV-1 Infection at the time when PrEP was initiated, they developed a resistant virus. It was noted that there were HIV-1 seroconverters who developed a resistance to the inhibitors being used. Following these, there have been such reported cases that have been detected in many parts of Africa

About this study, there was no proof of medically substantial increase in serum creatine for HIV-1 seronegative persons. Before enrollment, the individuals did not have any pre-existing renal impairment. Further studies need to be explored about safety of TDF based PREP, a proximal function of the renal tube and the mineral bone density. In addition to this measures need to be established to enhance protection in pregnancy, breastfeeding, and young ladies women amid whom HIV infection rates are elevated.

Antiretroviral treatment provides a substantial HIV transmission protection for serodiscordant couples though the protection is not usually complete since 26-32% of HIV acquirement in the serodiscordant spouse are from outside couples. It is evident that Strategies need to be established to guide in decisions regarding maximum timing and targeting of medication and PrEP for decreasing HIV frequency within partners. The mentioned strategies may prove to be essential especially to couples seeking to conceive and bear children. Despite the deployment of new approaches, some have been set such PrEP prevention approach for healthy persons with couples who do not know their HIV status or those that are HIV positive but are yet to initiate antiretroviral therapy. Conclusively this study emphasized the importance of HIV-1 synergistic prevention benefits of ongoing counseling, couple HIV testing and other HIV deterrence services together with PrEP for decreasing HIV risk in heterosexual couples. For PREP to be executed as a communal health strategy clinical monitoring will be required, provision for ensuring access and adherence to antiretroviral psychotherapy for HIV positive persons.

The discussion based on the research of HIV transmission risk factors between serodiscordant couples is as follows: HIV is more likely to be transmitted by men to their wives, therefore, making married women to be at high risk of HIV transmission. Results suggested that within south India partners engage in unprotected sex even upon knowing their HIV status. It was clear that the patients that higher viral loads were at a higher chance of transmitting HIV to their seronegative partner. The major risk factor for transmission among heterosexual partners is the Herpes simplex virus type 2. The study showed that a considerable number of patients who at enrollment presented to have the virus stated previously (Herpes simplex type 2) the prevalence genital Herpes simplex virus type 2 was very high. To curb this clinician ought to conduct routine Herpes simplex screening during clinical evaluation of the infected persons. In addition to this prophylactic therapy can deploy to reduce the risk of HIV transmission. The study was also basing if alcohol is the main contributor to the transmission of HIV. It was evident that close 33% of the patients that were infected by their spouse were regular consumers of alcohol. Alcohol use leads to decreased use of condom and thus a greater risk of HIV spread. Preventive measures such as prophylactic intervention and use of ARTs need to be deployed to curb the risk of HIV transmission. Other preventive measures include couple focus interventions and counseling as well. Frequent STIs, low condom use are some of the major factors that pose a high risk for HIV transmission. It is crucial to note that women face a significant challenge since they are at a higher risk for HIV infection due to breastfeeding, conception pregnancy and the tissue disposition of the PrEP.

Methods in which adherence is measured were described from the review of the current concepts of PrEP. Considerably self-reporting provides information that is overestimated due to bias though the method is readily available and it is cheap. A method that is accurate is objective measures though it is expensive. In studies such as the IPrEX it was found out that self-reported adherence measures were not useful in differentiating participants that had or didn’t have detectable tenofovir. SMS is a better way to improve self-reporting. To reduce bias questions can be administered whereby social desirability bias is eliminated through anonymity in comparison to one-on-one interview. The method was used in partners PrEP study where adherence and concurrent sexual behavior were monitored. MEMS caps is the widely used method in most projects. Day to day patterns of adherence is determined to evaluate alignment and the risk of HIV acquisition. Other methods include the Wisepill which is a wireless electronic monitoring system. The method enables monitoring adherence in real time and can also be used for enhanced counseling. To support PrEP adherence interventions such as enhanced counseling are deployed. A behavioral therapy which constitutes problem-solving and motivational interview is an approach that is commonly used. This approach is known as LifeSteps.

The method PrEP delivery faces some challenges among HIV serodiscordant couples. The challenges comprise of acceptability of PrEP. Primarily acceptance will depend on the health care providers, administrators, policymakers and the users, in this case, serodiscordant couples. Acceptance majorly was termed as the readiness to utilize or prescribe PrEP depending on the need or the predisposing features. The major challenge facing this method in the prevention of HIV is that most people are not aware of it. For example, in the US a research review conducted by Young and McDaid on acceptance of ART for preventing HIV there was no published records that indicated acceptability of PrEP among couples in a serodiscordant relationship in the US. Although in other places such as Africa and China studies have shown that the degree of acceptance and readiness to utilize PrEP is high amongst persons in a serodiscordant relationship. The major concern among couples in a serodiscordant relationship especially in the US is concern about side effects, stigma, costs and also have the burden of being on medication daily. Relationship factors such as intimacy and desires to conceive also affect the acceptability of oral PrEP. For example, a telephone survey in the US indicated that there was high acceptability for PrEP among women.

Another challenge facing use of PrEP among serodiscordant couples is the concern on conception or contraception. Delivery of PrEP can be presented as an opportunity and as a barrier to individuals who wish to conceive without transmission of the HIV. When PrEP preconception strategy is implemented during conception, and during pregnancy, the risk of HIV transmission is reduced. There is limited evidence supporting the existence of adverse effects of PrEP on infants. The other prevention technique of HIV transmission during conception and pregnancy include sperm washing which involves the intrauterine insemination. The strategy is applicable when the husband is a HIV positive individual and the HIV transmission is low. How the approach faces a significant setback since it expensive and not readily available in most public healthcare providers. Self-insemination can be considered when the wife is a HIV infected as it minimizes the transmission of HIV virus to the healthy partner. The risk is eliminated through avoiding contact with genital fluids of the infected partne (Johnsen, et al. 2017). Additionally, the cost of the drug is a huge challenge that is faced in PrEP. Estimates show that the annual cost of the drug is $ 17,000 per patient. The figure poses a big challenge to many couples given that most of the affected persons are usually economically disadvantaged. Measures need to deployed to reduce the gap. Funding by the government can prove to be beneficial in reducing the gap of cost.

Adherence to PrEP is another profound challenge faced in PrEP delivery which makes it necessary to understand the various rates at which different people conform to PrEP use. Problems facing adherence need to be identified and solutions provided to ensure a long-term success for this strategy. Some of the challenges associated with adherence include; availability of PrEP, the lifestyle of the participants, awareness or existence of abuse and violence in a relationship. Findings especially those conducted in Africa have indicated that participants who experience physical abuse from their partner frequently indicate a low adherence to PrEP. (Choopanya, et al. 2013). The phenomenon is associated with stress or the neglecting acts of not taking medication. Also, factors such as stigmatization due to use of PrEP may hinder adherence rates among various persons because some participants are overwhelmed by the fear of being exposed to other people. It is, therefore, a significant challenge in the society to people using PrEP thus the need to come up with measures that will ensure receptiveness for PrEP. Sensitization programs need to be established to educate the participants taking PrEP concerning the outcomes of low adherence to PrEP. For instance, they need to understand that one of the consequences for not following the PrEP medication is the high susceptibility rates to HIV infection and that those participants who acquire HIV face the risk of developing resistance to PrEP. A possible measure that would reduce stigmatization is making this strategy of PrEP delivery a mandatory health delivery. Studies also indicate that in areas associated high incidence for HIV, there is a high likelihood of people refusing to access the treatment of or get tested for HIV. People fear discrimination and thus decide to avoid the services. Therefore, providing PrEP as medication for any other disease patients, one must first weigh the benefits and risks then decide whether to take the medication. Guidelines further ensure to the patient that testing and treatment for HIV is not voluntary. Other measures that would provide high adherence include; monitoring alongside counseling and testing for HIV, and this should be done routinely. The approach ensures more individuals become more interactive with health care services and also are followed up. The proper strategy to implement monitoring would be via health professionals who would provide support by keeping in contact with the participants. Sexual health cares can be deployed for delivery of PrEP. Also, through health promotions schemes, it is possible to extend and ensure access to the services especially in rural areas where demand for PrEP is high, but the availability is very low (Kim , et al. (2010). Trained personnel on HIV prevention can visit the communities in rural areas and provide education on HIV and also provide PrEP to those that are at a substantial HIV risk in a manner that is culturally sensitive. Awareness strategies such as social marketing campaigns which not only create awareness but also reduce stigmatization and ensure acceptability for PrEP also need to be enacted. Clinical guidance among participants using PrEP need to be sensitized for community sensitization that PrEP is for use within a given timeline especially when individuals are at high risk of getting infected with HIV. Also, the clinical guidance makes the participants understand safety, effectiveness, and sustainability of PrEP. The strategies mentioned above foster a high level of adherence to PrEP amongst users. Different studies have shown there exists a strong correlation between PrEP effectiveness and daily adherence. Couples that are in a serodiscordant relationship are encouraged to use antiretrovirals (ART drugs) for the HIV infected partner for early treatment in order to curb the chances for HIV transmission combined with the use of daily oral PrEP for the uninfected partner. It is essential to sensitize PrEP use is an additional HIV prevention measure to avoid displacement of other prevention methods such as the use of condoms and STI treatment. Moreover, it is critical to ensure that PrEP users have easy access to the drugs to provide high levels of adherence.

The encouragement and improvement of adherence of PrEP amongst PrEP users depend on specific strategies that have been found useful, and these include motivational interviews, group sessions and support groups as well as educational sessions (Suliman, 2014). Motivational interviews usually entail individual counseling and face to face discussions. Group sessions, on the other hand, involve talks from various guests or group counseling sessions where participants discuss collectively or with each other. Furthermore, other methods that can be used to improve adherence include the SMS reminders. Motivational interviews, group discussions, and continuous education are the methods that can prove to be most useful for the users of PrEP. Even though these methods are commonly deployed in clinical trials, some of them are applied in the broader population for individuals using PrEP to encourage and improve adherence. Recent research indicates that the low adherence to PrEP is connected to the high resistance incidences to the drug. It is important to note that resistance to PrEP can only occur if the participant gets infected with HIV and continues to use PrEP since PrEP is intended for use by HIV uninfected persons. Thus, there is need to ensure there exist delivery systems that continuously check the HIV status of the individuals who are taking and those that wish to start using PrEP. Mathematical models developed indicate that most resistance for PrEP usually occur if participants do not adhere entirely to the treatment and this has an effect of having a population with high resistance rate to PrEP rather than having prevented new HIV infections through treatment method.

Study findings indicate that certain participants have a negative attitude towards the drug due to the belief that the delivery of the drug involves making a complex choice (Mahapatra, 2016). The people's perception is attributed to the fact that the applied strategy requires continuous testing and daily adherence to the medications. Individuals are forced to change their lifestyle to adapt to the medical care provision. Therefore, such side effects are the primary concern and participants ought to seek other methods of HIV prevention rather than face the risks of experiencing the consequences that are associated with the use of PrEP. Another factor that is perceived by the participants is the notion that this strategy encourages engagement in sexual activities with risky partners. The method seeks to sustain serodiscordant relationships, but some of the participants believe that the HIV negative partner is at a high risk for HIV infection. Moreover, the fact that this strategy poses a substantial burden especially in women is demonstrated by the point that some of the participants expressed that women have much responsibility in health issues concerning sex such as hormonal birth control methods (Sagaon-teyssier, et al. (2016). Participants argued that taking the pills, use of condoms since PrEP would not prevent against transmission of STIs alongside PrEP testing, and birth control methods were a significant burden to bear for women. The technique for PrEP use was also perceived to encourage unprotected sex since people might not view the importance of using condoms. Despite the strategy of PrEP delivery having some contrasting views, there were numerous indications of positive opinions on this approach. The perceived advantages include: the method is female-controlled thus women can protect themselves against HIV infection and are necessary not required to be dependent on the male partners for condom use. The technique being female-controlled is beneficial to ladies especially those that are in unstable relationships since the risk for HIV infection is significantly reduced. The strategy is also very effective for women who have risky partners (men who are abusive, have other sex partners or do not prefer to use condoms). PrEP use protects women who are in such insecure or unhealthy relationships. The most viable individuals who are encouraged to deploy this strategy are couples who are in a serodiscordant relationship. The measure promotes pregnancy as the risk for HIV transmission is significantly reduced. The delivery and use of PrEP is an empowerment to women. It is the only prevention strategy that is female-controlled other than the use of female condoms. The approach provides self-efficacy to women about their sexual health. Considerably, though PrEP is an efficient method in preventing HIV transmission among serodiscordant couples, other preventive measures should not be ignored (Mahabeer, et. al. 2011). They include condom use, for example, since PrEP does not offer protection against sexually transmitted diseases. The alternative methods for prevention are ART for individuals living with HIV, male circumcision and reducing the number of sexual partners. Hence, it advisable to combine PrEP with several preventive measures in order achieve maximum protection. There is also need to ensure awareness of using PrEP techniques to curb the spread of HIV infection. Studies have revealed that a significant percentage of individuals are aware of this method, however, among women, awareness needs to be emphasized through the provision of efficient and provision of safe HIV- prevention methods (Karnoski & Haggerty, 2017).

More research needs to be conducted to examine long-term safety, clinical monitoring, and adherence to PrEP. Moreover, the scope of the studies can also cover the suitable approaches of PrEP delivery, testing mechanisms for individuals who get infected while under medication and the assessment of risk compensation and drug resistance. Additionally, more research can help establish new transition mechanisms for persons who stop using the drug, however, successful delivery of PrEP will require an understanding of the factors facilitating implementation. Factors such as characteristics of clinical sites, resources PrEP policies, user attitude and characteristics influence outcomes of PrEP. Also, the dynamism of relationships among serodiscordant couples affects the implementation of PrEP. Clinics specialized in HIV such as the STI health centers and family planning clinics are the appropriate sites for delivery of PrEP. The sites are suitable since it is possible to accord treatment for both couples who are HIV infected and those who are HIV negative (Higgins, 2011). Even though the main set back is that they treat HIV-negative persons thus the observed stigma among participants who wish to initiate PrEP use. It is also difficult to identify couples who are in a serodiscordant relationship and maintain an open communication with the participants thus PrEP providers need to develop ways in which they can identify, engage, communicate and provide care to potential PrEP users together with their infected partner (Grant, 2010). In regard to the above facts, it is evident that more research need to be conducted in order to ascertain the factors that inhibit adherence as well as the appropriate timing for dosing and create optimal methods for monitoring adherence. Also, there is need to create strategies that guide the testing for adherence and counseling interventions for the serodiscordant couples who are under PrEP medication. Researchers also need to establish the safety of PrEP among heterosexuals such as persons with chronic diseases or those with mental health issues, women who take hormonal contraceptives and persons taking nephrotoxic drugs. Furthermore, scholars in this field need to evaluate PrEP side effects and the associated health risks. Also there is need to develop strategies that guide in testing for adherence and counseling interventions for the heterodiscordant couples who are under PrEP medication. Researches also need to establish safety of PrEP among heterosexuals such as persons with chronic diseases or those with mental health issues, women who take hormonal contraceptives and persons taking nephrotoxic drugs. In addition researches should evaluate PrEP side effects and the associated health risks.

Conclusion

Methods that proved to be significant in deploying PrEP were mouth TDF/ FTC and TDF. They provide substantial protection against HIV-1 for heterosexual men and women. There is need to sensitize wide-scale implementation for this delivery to HIV negative individuals within HIV serodiscordant spouses. The table below displays the recommended medication for oral PrEP.

Despite PrEP proving to an effective method for prevention of HIV, safety is a primary concern too. This is due to toxicity risks concerns of ART in uninfected persons following known toxicity of ART in HIV infected persons. The side effects of TDF or FTC/TDF include loss of bone mineral density, potential kidney injury, or gastrointestinal effects. This occurs after a long-term use of the drugs. In spite of this limitation putting the benefits are considered to surpass adverse outcomes of the drugs. There is need to ensure awareness of using PrEP measures to curb HIV. Studies have revealed that a meager percentage of individuals are aware of this method. Among women, knowledge needs to be sensitized through the provision of adequate and provision of safe HIV- prevention methods. The significant challenge being high risk due to tissue disposition of the drug, conception, pregnancy and breastfeeding factors. Despite the fact that women being at high risk of contracting HIV PrEP has been recommended for use by anyone who is at high-risk for acquiring HIV. Notably poor adherence of PrEP may have more significant consequences in women than in men. Biological factors in women such as genital mucosa immaturity, sexually transmitted infections, high partner viral loads or hormonal effects may influence adherence to PrEP. It has been observed that adherence to PrEP is better with daily dosing. There is the need for medication education and adherence counseling to support regular use of PrEP which includes helping patients establish concrete dosing routines.

Couple-based interventions models play a great deal in preventing HIV transmission in seronegative partners. In conjunction with other preventive measures prompt sexually transmitted infections medications and publicizing the used condom are potential measures that actively reduce the risk of HIV transmission.

Statistical results have shown that when PrEP is taken consistently the risk of transmission of HIV to people who are at high risk is reduced by 92%. Despite this positive outcome the drug has to be taken consistently otherwise it will be ineffective. To ensure its effectiveness, the couples in a serodiscordant relationship must ensure the drug is taken every day, and a follow a follow up of every three months maintained with the health care providers. This is essential to monitor any side effects experienced, test for HIV and any sexually transmitted infections and also receive a prescription for the drugs. It is recommendable for couples who are in the hetero-discordant relationship be counseled on PrEP. This counseling can constitute:

· Giving information on PrEP and assisting in determining if the method is acceptable for the couple. This is important since PrEP is usually applicable for HIV-negative persons that are high risk. Therefore an HIV risk assessment needs to be conducted to evaluate the situation since the method has negative side effects and is very expensive too. Discussing this with the couples can help come up with an informed decision on which strategy to deploy.

· Assisting how to find a health care provider who will prescribe PrEP and how the cost will be covered. There is need to encourage the clients to discuss the PrEP with their family doctors who provide prescription for ART to the partner infected with HIV. It is also essential for the clients to contact their insurance companies to know if the cost is covered.

· Provision of support with adherence and also engagement in PrEP services whereby it is possible to explore any challenges to adherence. Additionally, it will be possible to evaluate ways in which the barriers can be overcome.

1. It is important to note that even PrEP is an efficient method in preventing HIV transmission among serodiscordant couples other preventive measures should not be ignored too. These include condom use for example since PrEP does not offer protection against sexually transmitted diseases. Other methods for prevention are ART for individuals living with HIV, male circumcision and reducing the number of sexual partners. Thus it advisable to combine PrEP with other preventive measures in order achieve maximum protection.

Even though statistical results indicated that gender dissimilarities for PrEP effectiveness were statistically insignificant, women need to take PrEP consistently to reach levels that offer genuine protection. Some findings indicated that women who took about four to five pills a week were at a higher risk of getting infected as compared men who did make the same dosage. Thus women need to more sensitive to their dosage to ensure consistent adherence to PrEP.

HIV prevention for couples who are in serodiscordant relationships can be more comfortable in comparison to individuals that are in other types of relationships. This is because the pairs can be able to motivate adopting an HIV prevention strategy to minimize the risk of HIV spread. Compared to individuals that are not in a serodiscordant relationship the perception of being at risk for HIV infection is low thus this reduces the chances of adopting a risk reduction strategy. Also being in the serodiscordant connection, it is possible to eliminate any uncertainties related to the HIV status of the partner. On the other hand, if one partner who is in the seroconcordant relationship is infected with HIV unknowingly risk of HIV transmission is very high since the viral load of the infected partner is elevated and possibly the couples are not using any preventive measures.

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STATUS OF ART AFTER FOLLOW UP

ART unknown Not on ART On ART(not virally supressed) On ART(unknown viral level On ART(virally supressed) 11.4 4.5999999999999996 8.2199999999999989 0.39 000000000000024 75.400000000000006

STATE

PERCENTAGE

CD4 COUNT DEPENDING ON THE DRUG USED

TDF FTC placebo 491 497 499

Drug deployed

CD4 count